IP Library Granted Patent US 7,164,008
Granted Patent B2
US 7,164,008 · App. 10/715,876 · Granted Jan 16, 2007

Isolated complexes of endotoxin and MD-2

Assignee: University of Iowa Research Foundation
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Quick Facts
Patent No.
US 7,164,008
App. No.
10/715,876
Granted
Jan 16, 2007
Kind
B2
Abstract

Applicants have produced and isolated water soluble complexes of endotoxin and MD-2.

Claims (24)

1. A purified complex consisting of one molecule of endotoxin bound to one molecule of MD-2.

2. The complex of claim 1 , wherein the endotoxin is a wild-type endotoxin.

3. The complex of claim 1 , wherein the endotoxin is a gram-negative bacterial endotoxin.

4. The complex of claim 3 , wherein the gram-negative bacterium is a Neisseria, Escherichia, Pseudomonas, Haemophilus, Salmonella , or Fraricisella bacterium.

5. The complex of claim 4 , wherein the gram-negative bacterium is Neisseria meningitidis, Escherichia coil, Pseudomonas aeruginosa, Haemophilus influenzae, Salmonella typhimurium , or Francisella tularensis.

6. The complex of claim 1 having a molecular weight of about 25,000.

7. The complex of claim 1 , wherein the complex is soluble in water.

8. The complex of claim 1 , wherein the complex binds to TLR4.

9. The complex of claim 1 , wherein the complex produces TLR4-dependent activation of cells.

10. The purified complex of claim 9 , wherein the complex is administered at a concentration of less than 1 nM produces a half maximal TLR4-dependent activation of cells.

11. The complex of claim 9 , wherein the complex is administered at a concentration of less than 30 pM produces a half maximal TLR4-dependent activation of cells.

12. A purified complex comprising endotoxin bound to MD-2, wherein the endotoxin is selected from the group consisting of hexa-acylated endotoxin, under-acylated endotoxin, penta-acylated endotoxin and tetra-acylated endotoxin.

13. The complex of claim 12 , wherein the purified complex consists of one molecule of endotoxin bound to one molecule of MD-2.

14. The complex of claim 12 , wherein the endotoxin is a tetra-acylated endotoxin.

15. The complex of claim 12 , wherein the endotoxin is a penta-acylated endotoxin.

16. The complex of claim 12 , wherein the complex produces less TLR4-dependent activation of cells when the endotoxin is under-acylated as compared to a complex comprising an endotoxin that is hexa-acylated.

17. The complex of claim 12 , wherein the endotoxin is under-acylated.

18. The complex of claim 12 , wherein the endotoxin is hexa-acylated.

19. A composition comprising a purified complex comprising endotoxin bound to MD-2, wherein the endotoxin is selected from the group consisting of hexa-acylated endotoxin, under-acylated endotoxin, penta-acylated endotoxin and tetra-acylated endotoxin and a pharmaceutically acceptable carrier.

20. The composition of claim 19 , wherein the endotoxin is hexa-acylated.

21. The composition of claim 19 , wherein the endotoxin is under-acylated.

22. The composition of claim 19 , wherein the endotoxin is a tetra-acylated endotoxin.

23. The composition of claim 19 , wherein the endotoxin is a penta-acylated endotoxin.

24. A composition consisting of the purified complex of claim 1 and a pharmaceutically acceptable carrier.

Assignments (3)
CONFIRMATORY LICENSE Recorded Feb 4, 2021
From: UNIVERSITY OF IOWA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 055220/0372 →
CONFIRMATORY LICENSE Recorded May 11, 2020
From: UNIVERSITY OF IOWA
To: NATIONAL INSTITUTES OF HEALTH
Reel/Frame 052626/0736 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2004
From: WEISS, JERROLD P.; GIOANNINI, THERESA L.; TEGHANEMT, ATHAMANE; SUBRAMANIAN, RAMASWAMY
To: UNIVERSITY OF IOWA RESEARCH FOUNDATION
Reel/Frame 014529/0224 →
Continuity (1)
Related Publication 20050106179A1 · May 19, 2005